A phase I study of sirolimus and bevacizumab in patients with advanced malignancies

Eur J Cancer. 2011 Jul;47(10):1484-9. doi: 10.1016/j.ejca.2011.02.017. Epub 2011 Mar 23.


Background: We performed a single institution, phase I study of sirolimus and bevacizumab, in order to determine the dose limiting toxicity (DLT) and recommended phase II doses.

Patients and methods: Eligible patients had previously treated advanced malignancies and were enrolled in three cohorts. Sirolimus 90 mg PO weekly (45 mg on days 1 and 2) was combined with bevacizumab 7.5mg/kg (cohort #1) or bevacizumab 15 mg/kg (cohort #2) IV q3weeks. Sirolimus 4 mg PO daily was combined with bevacizumab 15 mg/kg IV q3weeks (cohort #3).

Results: Twenty-eight patients enrolled. The most common tumour types were colorectal (21%), head/neck (14%), and renal cell (11%). No DLTs were observed in cohorts #1 (4 patients) and #2 (12 patients), while two DLTs (grade 3 confusion and grade 3 fatigue) were observed in the first six patients in cohort #3 (12 patients). The most common grade 3 toxicities were fatigue (18%), hypertension (14%) and anorexia (11%). There were no responses, but one patient has had stable disease for 78 weeks.

Conclusions: The combination of sirolimus and bevacizumab at full doses is tolerable in the majority of patients. The availability and cost of sirolimus compared with other mTOR inhibitors make this an attractive agent to combine with bevacizumab.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Bevacizumab
  • Carcinoma, Renal Cell / drug therapy
  • Cohort Studies
  • Colorectal Neoplasms / drug therapy
  • Female
  • Humans
  • Kidney Neoplasms / drug therapy
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasms / drug therapy*
  • Neoplasms / immunology
  • Sirolimus / administration & dosage*
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • Treatment Outcome


  • Antibodies, Monoclonal, Humanized
  • Bevacizumab
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Sirolimus